基于JAK/STAT信号通路探讨夏枯草提取物对间变性大细胞淋巴瘤的作用及机制研究  

Exploration of the Effect and Mechanism of the Extract of Spica Prunellae for Treatment of Anaplastic Large Cell Lymphoma Based on JAK/STAT Signaling Pathway

作　　者：李伟明[1] 薛伟丽 付晓瑞[2] 孙振昌[2] 张明智[2] LI Wei-ming;XUE Wei-li;FU Xiao-rui;SUN Zhen-chang;ZHANG Ming-zhi(Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;The First Affiliated Hospital of Zhengzhou University,Zhengzhou 410105 Henan,China)

机构地区：[1]河南中医药大学,河南郑州450006 [2]郑州大学第一附属医院,河南郑州410105

出　　处：《中医肿瘤学杂志》2022年第2期35-42,34,共9页Journal of Oncology in Chinese Medicine

基　　金：河南省中医药管理局课题(编号:2018ZY2105);河南中医药大学博士基金(编号:BSJJ2020-03);河南中医药大学苗圃工程(编号:MP2020-25)。

摘　　要：目的研究夏枯草提取物对间变性大细胞淋巴瘤作用及机制。方法收集2011年到2021年淋巴瘤患者的病历资料,详细筛选并规范化处理,将其录入数据挖掘系统“中医传承辅助平台V2.5”,建立处方数据库,采用频数分析的方法,对处方用药进行研究。体外培养Karpas299细胞,采用CCK8的方法计算不同浓度的夏枯草提取物在不同时间对Karpas299细胞增殖的抑制作用。采用流式细胞技术检测夏枯草提取物对Karpas299细胞凋亡的影响。采用Western blot技术检测夏枯草提取物对Karpas299细胞JAK3、STAT3、Bcl-2、Bax凋亡蛋白表达的影响。通过BALB/c裸鼠构建间变性大细胞淋巴瘤动物模型,观察夏枯草提取物对ALCL的作用效果。结果夏枯草提取物可显著抑制Karpas299细胞的增殖,并且随着药物浓度的增高,抑制作用明显增强,并且随着药物作用时间的延长,抑制作用明显增强,其48小时抑制Karpas299细胞增殖的药物IC50为(33.2±1.8)ug/ml,通过流式细胞仪检测夏枯草提取物作用Karpas299细胞后细胞凋亡的影响,通过Western blot技术检测夏枯草提取物作用Karpas299细胞后,p-JAK3蛋白表达下降、p-STAT3蛋白表达下降、凋亡蛋白Bcl-2表达降低、Bax表达升高。动物实验同时证明,夏枯草提取物可抑制瘤组织的生长,与空白对照组相比,其中夏枯草提取物组、长春新碱组瘤组织体积增大明显减少,P<0.01(P=0.0094,P=0.0091),降低瘤组织p-JAK3蛋白、p-STAT3蛋白和Bcl-2蛋白的表达,促进瘤组织Bax蛋白的表达。结论夏枯草提取物抑制Karpas299细胞增殖可能与抑制JAK3/STAT3进而促进凋亡有关。Objective To investigate the effect and mechanism of the extract of Spica Prunellae for the treatment of anaplastic large cell lymphoma(ALCL).Methods Medical records of lymphoma patients from 2011 to 2021 were collected,and the clinical information of the patients were screened in details and processed in a standardized manner.The records were input into the platform of Traditional Chinese Medicine Inheritance Support System(V2.5),and then the prescription database was established.The prescription medication was studied by frequency analysis.Karpas299 cells were cultured in vitro for the observation of the inhibitory effect of different concentrations of Spica Prunellae extract on the proliferation of Karpas299 cell at different times with CCK8 method.Flow cytometry was adopted to detect the effect of Spica Prunellae extract on Karpas299 cell apoptosis,and Western blotting analysis was utilized to detect the effects of Spica Prunellae extract on the expression of apoptotic proteins of JAK3,STAT3,bcl-2 and Bax in Karpas299 cells.The ALCL animal model was established with BALB/c nude mice for the evaluation of the effect of Spica Prunellae extract on ALCL.Results Spica Prunellae extract can significantly inhibit Karpas299 cell proliferation,and the inhibition was enhanced obviously with the increase of the drug concentration and with the prolongation of drug action time.The IC50 of Spica Prunellae extract on inhibiting Karpas299 cell proliferation within 48 hours was(33.2±1.8)ug/mL.The results of flow cytometry and Western blotting analysis showed that the expression of apoptotic protein p-JAK3,p-STAT3 and Bcl-2 was decreased and the expression of Bax was increased.The results of the animal experiments also showed that Spica Prunellae extract inhibited the growth of tumor tissues.In comparison with blank control group,the tumor mass in Spica Prunellae extract group and vincristine group was significantly decreased(P=0.0094,P=0.0091),the expression of p-JAK3,p-STAT3 and Bcl-2 protein in tumor tissues was decreased,

关 键 词：夏枯草提取物 Karpas299细胞 JAK/STAT信号通路 BALB/C裸鼠 

分 类 号：R733.4[医药卫生—肿瘤] R730.52[医药卫生—临床医学]